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Objective: This study aimed to evaluate the in vitro antibacterial effects of lysozyme‐chitosan oligosaccharide conjugates (LYZOX) against Streptococcus gordonii and Porphyromonas gingivalis. Materials and Methods: Planktonic S. gordonii and P. gingivalis were treated with various concentrations of LYZOX for 10 min. The treated bacteria were incubated on trypticase soy agar plates, and colony‐forming unit (CFU) was calculated. The antibacterial effect of LYZOX was compared with that of lysozyme, chitosan, physiological saline, and benzalkonium chloride solution. Cell morphology before and after LYZOX treatment was observed using a scanning electron microscope (SEM). The antibacterial effect of LYZOX with decanoic acid against the biofilm‐like bacteria was also examined via crystal violet staining. The Kruskal–Wallis test and post hoc Dunn tests were performed to compare the difference in antibacterial activity of each treatment. Results: Bacterial CFU numbers were reduced after LYZOX treatment in a concentration‐dependent manner. The reduction in CFUs was smaller for corresponding concentrations of chitosan or lysozyme alone. SEM analyses revealed bacterial cells shrank following LYZOX treatment. The combined use of LYZOX and decanoic acid yielded an even higher antibacterial effect against bacterial biofilms. Conclusion: LYZOX exhibits antibacterial activity against two periodontal bacteria and may be a promising plaque control agent. [ABSTRACT FROM AUTHOR]